Dulaglutide
GLP-1 receptor agonist · Antidiabetic · Fc-fusion biologic
Dulaglutide
Trulicity
Dulaglutide is a weekly subcutaneous GLP-1 receptor agonist developed by Eli Lilly, marketed as Trulicity since September 2014.[2] Structurally distinct from the acylated peptide GLP-1 RAs (semaglutide, liraglutide), dulaglutide is an Fc-fusion biologic — its long half-life comes from FcRn-mediated recycling rather than albumin binding.[1]
Dulaglutide's principal clinical distinction is the REWIND trial, in which dulaglutide reduced major adverse cardiovascular events by 12% in T2DM patients including a majority with no prior cardiovascular disease — making it the first GLP-1 RA to demonstrate cardiovascular benefit in primary prevention.[3]
Avoid. Animal embryofetal toxicity is documented.[2] Discontinue at least 1 month before planned conception due to the ~5-day half-life. The pen contains no preservatives — single-dose only.
GLP-1 receptor agonist · Semaglutide · Liraglutide · Tirzepatide · Exenatide · Type 2 diabetes mellitus
Experience
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Problems
<indication ref="diabetes-type-2" author="MDElliottMD"/> <indication ref="cv-risk-t2dm" author="MDElliottMD"/>
+ Add a problemTitration strategies
Trulicity — standard T2DM titration0
0.75 mg SC weekly (starting and minimum effective dose)
→ 1.5 mg SC weekly × ≥4 weeks (most common maintenance) → 3 mg weekly × ≥4 weeks if additional HbA1c reduction needed → 4.5 mg weekly (max)[2]
The 0.75 mg starting dose is therapeutic (unlike the non-therapeutic ramps with semaglutide and tirzepatide). Most patients escalate to 1.5 mg within the first month.Effects
- Early satiety (less pronounced than with semaglutide/tirzepatide at equipotent HbA1c reduction)[citation needed]
- Nausea — usually mild-to-moderate, peaks in first 2–4 weeks[2]
- Diarrhea / constipation[2]
- Abdominal pain[2]
- Decreased appetite[2]
- Injection-site reactions — uncommon, generally mild[2]
GI tolerability is generally considered modestly better than weekly exenatide and comparable to or slightly better than weekly semaglutide at equivalent glycemic effect.[citation needed]
Pharmacokinetics
The Fc-IgG4 fusion confers protection from renal filtration (~63 kDa, well above the glomerular cutoff) and triggers FcRn-mediated recycling, producing a terminal half-life of ~120 hours.[1][2] Cleared by proteolytic catabolism; no CYP-mediated metabolism. No dose adjustment for renal or hepatic impairment.[2]
The large molecular size limits both injection-site dispersion and oral bioavailability — dulaglutide cannot be formulated for oral use.Pharmacodynamics
At maintenance doses:
- HbA1c reduction of ~0.8–1.5 percentage points (1.5 mg/wk) and ~1.6–1.9 (4.5 mg/wk) in T2DM[4]
- Weight loss of ~2–5 kg, dose-dependent[4]
- 12% relative risk reduction in MACE (REWIND)[3]
- Modest SBP reduction (~1–2 mmHg)[2]
Interactions
No interactions reported yet.
Pregnancy and lactation
Monitoring
- Baseline: HbA1c, weight, BP, renal function, lipid panel
- Personal or family history of MTC or MEN2 — contraindicated, do not start[2]
- Every 3 months for first year: HbA1c, weight, GI tolerability, signs of pancreatitis or gallbladder disease
- Annual: renal function, lipids
- Pre-procedure: hold weekly dose ≥7 days before any planned anesthesia[5]
Patient counseling
- Use the pre-filled pen as directed; the needle is hidden — patients do not see it. This is often the preferred GLP-1 RA for needle-averse patients.[citation needed]
- GI side effects peak in first 2–4 weeks, then attenuate.[2]
- If a weekly dose is missed: take within 3 days; if >3 days, skip and resume on the next regular day.[2]
- Surgery: hold dose 7 days pre-op.[5]
- Pregnancy planning: stop ≥1 month before trying to conceive.[2]
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Relevant Literature
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See also
References
- ↑ 1.0 1.1 1.2 1.3 Glaesner W, Vick AM, Millican R et al. (2010). Engineering and characterization of the long-acting glucagon-like peptide-1 analogue LY2189265, an Fc fusion protein. Diabetes Metab Res Rev 26(4):287–96. doi:10.1002/dmrr.1080
- ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 2.16 2.17 2.18 2.19 2.20 2.21 2.22 2.23 2.24 US FDA. Trulicity (dulaglutide) prescribing information. Eli Lilly. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/125469s044lbl.pdf
- ↑ 3.0 3.1 Gerstein HC et al. (2019). Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND). Lancet 394(10193):121–30. doi:10.1016/S0140-6736(19)31149-3
- ↑ 4.0 4.1 Frias JP, Bonora E, Nevarez Ruiz L et al. (2021). Efficacy and safety of dulaglutide 3 and 4.5 mg versus 1.5 mg in metformin-treated patients with type 2 diabetes (AWARD-11). Diabetes Care 44(3):765–73. doi:10.2337/dc20-1473
- ↑ 5.0 5.1 Kindel TL et al. (2024). Perioperative GLP-1 receptor agonist safety guidance. Surg Obes Relat Dis 20(12):1183–8.
[[File:Fc-fusion construct: two identical GLP-1 analog peptides (each modified at positions 8, 22, 36 for DPP-4 resistance and reduced immunogenicity) linked to a human IgG4 Fc fragment via a small glycine-rich peptide linker. The Fc tail drives the long half-life through FcRn recycling.[1]|frameless|240px|alt=Structure of Dulaglutide]]
Summary
Classes
GLP-1 receptor agonist · Antidiabetic · Fc-fusion biologic
Pharmacy
Starting dose
0.75 mg SC weekly[2]
Preparations
Pre-filled single-dose pen: 0.75 / 1.5 / 3 / 4.5 mg[2]
US FDA Max
4.5 mg/wk SC[2]
Pharmacology
Routes
Subcutaneous (abdomen, thigh, upper arm)[2]
Onset
Glycemic effect within days; near-maximal HbA1c effect by 4 weeks at any given dose[2]
Duration
~7 days (weekly dosing)[2]
Half-life
~5 days (~120 h)[2]
Bioavailability
SC ~47%–65%[2]
Pregnancy
Avoid. Discontinue at least 1 month before planned pregnancy. Animal data show embryofetal harm.[2]
Legal status
Rx-only;[2] not a controlled substance
Purported mechanism
Selective long-acting agonist of the GLP-1 receptor. The Fc-IgG4 structure differentiates it pharmacokinetically (large protein cleared by FcRn-mediated recycling rather than albumin binding) but the receptor pharmacology is the standard GLP-1 RA profile.[1]